Effects of plant protease inhibitors (Pep-3-EcTI, Pep-BbKI, and Pep-BrTI) versus corticosteroids on inflammation, remodeling, and oxidative stress in an asthma-COPD (ACO) model.

The peptide derived from E. contortisiliquum trypsin inhibitor (Pep-3-EcTI), peptide derived from kallikrein inhibitor isolated from B. bauhinioides (Pep-BbKI), and B. rufa peptide modified from B. bauhinioides (Pep-BrTI) peptides exhibit anti-inflammatory and antioxidant activities, suggesting their potential for treating asthma-chronic obstructive pulmonary disease (COPD) overlap (ACO). We compared the effects of these peptides with dexamethasone (DX) treatment in an ACO model. In this study, 11 groups of male BALB/c mice were pre-treated under different conditions, including sensitization with intraperitoneal injection and inhalation of ovalbumin (OVA), intratracheal instillation of porcine pancreatic elastase (ELA), sensitization with intraperitoneal injection, and various combinations of peptide treatments with Pep-3-EcTI, Pep-BbKI, Pep-BrTI, dexamethasone, and non-treated controls (SAL-saline). Respiratory system resistance, airway resistance, lung tissue resistance, exhaled nitric oxide, linear mean intercept, immune cell counts in the bronchoalveolar lavage fluid, cytokine expression, extracellular matrix remodeling, and oxidative stress in the airways and alveolar septa were evaluated on day 28. Results showed increased respiratory parameters, inflammatory markers, and tissue remodeling in the ACO group compared to controls. Treatment with the peptides or DX attenuated or reversed these responses, with the peptides showing effectiveness in controlling hyperresponsiveness, inflammation, remodeling, and oxidative stress markers. These peptides demonstrated an efficacy comparable to that of corticosteroids in the ACO model. However, this study highlights the need for further research to assess their safety, mechanisms of action, and potential translation to clinical studies before considering these peptides for human use.

Effect of Alpha-1 Antitrypsin and Irisin on Post-Exercise Inflammatory Response: A Narrative Review.

Physical activity has a positive effect on human health and emotional well-being. However, in both amateur and professional athletes, training poses a risk of acute or chronic injury through repetitive overloading of bones, joints, and muscles. Inflammation can be an adverse effect of intense exercise caused by several factors including oxidative stress. The present narrative review summarizes current knowledge on inflammatory markers induced by physical exercise. Post-exercise recovery may reduce inflammatory responses and is key to effective training and adaptation of muscle tissues to sustained physical exertion.

Efficacy and safety of evolocumab in elderly patients with high-risk cardiovascular diseases / 中华老年心脑血管病杂志

Objective To explore the efficacy and safety of evolocumab in elderly patients with high-risk cardiovascular diseases.Methods A total of 153 patients with poor lipid control after conventional statin therapy who were hospitalized in the cardiologic departments in the First,Sec-ond,Sixth and Eighth Medical Centers of Chinese PLA General Hospital from November 2019 to November 2022 were included,and divided into non-elderly group(＜60 years old,46 cases),eld-erly group(60-74 years old,66 case)and very elderly group(≥75 years old,41 cases).They were all given evolocumab treatment according to guidelines.Another 50 over-75-year-old patients with high-risk cardiovascular diseases and poor lipid control who were hospitalized in the above cardiologic departments during the same period were treated with a statin drug combined with ezetimibe,and served as conventional treatment group(control group).The baseline clinical data and the blood indicators at 4th and 12th week after drug administration,and the occurrence of ad-verse drug reactions and major adverse cardiovascular events(MACE)within 12 weeks were com-pared among the groups.Results The levels of LDL-C and TC were significantly decreased in the three evolocumab treatment groups at 4 and 12 weeks after medication when compared with the baseline values(P＜0.05,P＜0.01),but there were no obvious differences in the 2 levels among the 3 groups at 12 weeks(P＞0.05).At the time point,no statistical difference was observed in the incidence of adverse events in the three groups(2.2％vs 3.0％vs 2.4％,P＞0.05).The levels of LDL-C and TC were decreased significantly in the very elderly group and the conventional treatment group at the 12th week when compared with the baseline levels(P＜0.05,P＜0.01),and the LDL-C level at the week was notably lower in the very elderly group than the convention-al treatment group(1.36±0.44 mmol/L vs 1.87±0.56 mmol/L,P＜0.01).But no difference was seen in the incidence of MACE between the 2 groups(12.2％vs 16.0％,P＞0.05),either in sur-vival rate between them(P=0.576).Conclusion For patients of all ages,evolocumab has good short-term efficacy in lipid control,and for those over 75 years old,the drug also shows good effi-cacy and sound safety.

Effects of a Peptide Derived from the Primary Sequence of a Kallikrein Inhibitor Isolated from Bauhinia bauhinioides (pep-BbKI) in an Asthma-COPD Overlap (ACO) Model.

(1) There are several patients with asthma-COPD overlap (ACO). A peptide derived from the primary sequence of a kallikrein inhibitor isolated from Bauhinia bauhinioides (pep-BbKI) has potent anti-inflammatory and antioxidant effects. Purpose: To investigate the effects of pep-BbKI treatment in an ACO model and compare them with those of corticosteroids. (2) BALB/c mice were divided into groups: SAL (saline), OVA (ovalbumin), ELA (elastase), ACO (ovalbumin + elastase), ACO-pep-BbKI (treated with inhibitor), ACO-DX (dexamethasone treatment), ACO-DX-pep-BbKI (both treatments), and SAL-pep-BbKI (saline group treated with inhibitor). We evaluated: hyperresponsiveness to methacholine, bronchoalveolar lavage fluid (BALF), exhaled nitric oxide (eNO), IL-1ß, IL-4, IL-5, IL-6, IL-10, IL-13, IL-17, IFN-γ, TNF-α, MMP-9, MMP-12, TGF-ß, collagen fibers, iNOS, eNO, linear mean intercept (Lm), and NF-κB in airways (AW) and alveolar septa (AS). (3) ACO-pep-BbKI reversed ACO alterations and was similar to SAL in all mechanical parameters, Lm, neutrophils, IL-5, IL-10, IL-17, IFN-γ, TNF-α, MMP-12 (AW), collagen fibers, iNOS (AW), and eNO (p > 0.05). ACO-DX reversed ACO alterations and was similar to SAL in all mechanical parameters, Lm, total cells and differentials, IL-1ß(AS), IL-5 (AS), IL-6 (AS), IL-10 (AS), IL-13 (AS), IFN-γ, MMP-12 (AS), TGF-ß (AS), collagen fibers (AW), iNOS, and eNO (p > 0.05). SAL was similar to SAL-pep-BbKI for all comparisons (p > 0.05). (4) Pep-BbKI was similar to dexamethasone in reducing the majority of alterations of this ACO model.

Coumarins as factor XIIa inhibitors: Potency and selectivity improvements using a fragment-based strategy.

Previously, we described weak coumarin inhibitors of factor XIIa, a promising target for artificial surface-induced thrombosis and various inflammatory diseases. In this work, we used fragment-based drug discovery approach to improve our coumarin series. First, we screened about 200 fragments for the S1 pocket. The S1 pocket of trypsin-like serine proteases, such as factor XIIa, is highly conserved and is known to drive a major part of the association energy. From the screening, we selected fragments displaying a micromolar activity and studied their selectivity on other serine proteases. Then, these fragments were merged to our coumarin templates, leading to the generation of nanomolar inhibitors. The mechanism of inhibition was further studied by mass spectrometry demonstrating the covalent binding through the formation of an acyl enzyme complex. The most potent compound was tested in plasma to evaluate its stability and efficacy on coagulation assays. It exhibited a plasmatic half-life of 1.9 h and a good selectivity for the intrinsic coagulation pathway over the extrinsic one.

Factor XII(a) inhibitors: a review of the patent literature.

Introduction: Blood coagulation factor XII (FXII) is an emerging and potentially safe drug target, which dysregulation is associated with thrombosis, hereditary angioedema, and (neuro)inflammation. At the same time, FXII-deficiency is practically asymptomatic. Industrial and academic institutions have developed a number of potential therapeutic agents targeting either FXII zymogen or its active form FXIIa for the treatment of thrombotic and inflammatory conditions associated with the activity of this enzyme.Areas covered: A short overview of the FXII(a) structure and function, underlining its suitability as a drug target, is given. The article reviews patents reported over the last three decades on FXII(a)-targeting therapeutic agents. These agents include small molecules, proteins, peptides, oligonucleotides, siRNAs, and monoclonal antibodies.Expert opinion: The performed analysis of patents revealed that many FXII(a) inhibitors are in the early preclinical stage, while several already showed efficacy in vivo animal models of thrombosis, sepsis, hereditary angioedema, and multiple sclerosis. Two anti-FXIIa agents namely tick protein Ir-CPI and monoclonal antibody CSL312 are currently in human clinical trials. The results of these trials and further studies of FXII(a) pathophysiological functions will encourage the development of new FXII(a) inhibitors.

Capillary electrophoresis as a fragment screening tool to cross-validate hits from chromogenic assay: Application to FXIIa.

In this study, a partial-filling affinity capillary electrophoresis (pf-ACE) method was developed for the cross-validation of fragment hits revealed by chromogenic factor XIIa (FXIIa) assay. Chromogenic assay produces false positives, mainly due to spectrophotometric interferences and sample purity issues. pf-ACE was selected as counter-screening technology because of its separative character and the fact that the target does not have to be attached or tagged. The effects of protein plug length, applied voltage and composition of the running buffer were examined and optimized. Detection limit in terms of dissociation constant was estimated at 400 µM. The affinity evaluation was performed close to physiological conditions (pH 7.4, ionic strength 0.13 mol L-1) in a poly (ethylene oxide)-coated capillary of 75 µm internal diameter x 33 cm length with an applied voltage of 3 kV. This method uncovered chromogenic assay's false positives due to zinc contamination. Moreover, pf-ACE supported the evaluation of compounds absorbing at 405 nm.

Evaluation of the Small Airways in Patients with Chronic Obstructive Pulmonary Disease and Alpha-1 Antitrypsin Deficiency.

Introduction: Small airways are not evaluated with traditional pulmonary function tests. The aim of this study was to evaluate the small airways in patients with chronic obstructive pulmonary disease (COPD) with a nitrogen washout test and to verify whether there is a difference between patients with COPD due to smoking and those with COPD due to alpha-1 antitrypsin mutation. Methods: Sixteen patients with mutation in the SERPINA1 gene and 45 patients with no mutation were included in this cross-sectional study. All pulmonary function tests, including the single breath nitrogen washout test, were performed for all patients and alpha-1 antitrypsin dosage was assessed with immunonephelometry. Results: A comparison of patients with COPD due to smoking and those with COPD due to smoking and mutation revealed a significant difference in closure volume (%), which was the poorest in the mutation group. In the group with COPD and mutation, there was an inverse correlation between smoking and closure volume (%). We also verified that similar to forced expiratory volume in the first second (FEV1), the phase III slope (%) and ΔN2 750-1250 mL (%) could be used to differentiate the severity of airflow limitation. Conclusion: Our results suggest that both variables, phase III slope and the ΔN2 750-1250 mL (%), could be related to COPD severity. Therefore, alterations at the distribution of the location of the emphysema could alter the results of closer volume and that the nitrogen washout test is more sensitive when compared to traditional pulmonary function test in evaluating COPD patients.

Factor XII/XIIa inhibitors: Their discovery, development, and potential indications.

Coagulation factor XII (FXII), a S1A serine protease, was discovered more than fifty years ago. However, its in vivo functions and its three-dimensional structure started to be disclosed in the last decade. FXII was found at the crosstalk of several physiological pathways including the intrinsic coagulation pathway, the kallikrein-kinin system, and the immune response. The FXII inhibition emerges as a therapeutic strategy for the safe prevention of artificial surface-induced thrombosis and in patients suffering from hereditary angioedema. The anti-FXII antibody garadacimab discovered by phage-display library technology is actually under phase II clinical evaluation for the prophylactic treatment of hereditary angioedema. The implication of FXII in neuro-inflammatory and neurodegenerative disorders is also an emerging research field. The FXII or FXIIa inhibitors currently under development include peptides, proteins, antibodies, RNA-based technologies, and, to a lesser extent, small-molecular weight inhibitors. Most of them are proteins, mainly isolated from hematophagous arthropods and plants. The discovery and development of these FXII inhibitors and their potential indications are discussed in the review.

Kallistatin correlates with inflammation in abdominal aortic aneurysm and suppresses its formation in mice.

BACKGROUND: Kallistatin (KS), encoded by SERPINA4, was suggested to play a protective role in many cardiovascular diseases. However, its role in the pathogenesis of abdominal aortic aneurysm (AAA) remains unclear. The aim of this study was to examine the potential association of KS with AAA pathogenesis. METHODS: We examined KS (SERPINA4) expression in human AAA by PCR, immunohistochemistry, western blotting, and enzyme-linked immunosorbent assay (ELISA) and analyzed correlations between kallistain and clinical data. We then analyzed the effect of recombinant KS on AAA formation and the Wingless (Wnt) signaling pathway in a mouse AAA model developed by angiotensin II (AngII) infusion to apolipoprotein E-deficient (ApoE-/-) mice. RESULTS: In AAA tissue samples, KS was significantly increased compared with samples from the control group (P<0.001, P<0.001, respectively). Clinically, decreased SERPINA4 expression in AAA tissue samples represented an increased rate of iliac artery aneurysm [odds ratio (OR): 0.017; P=0.040]. And decreased plasma KS level represented a high risk for rupture (OR: 0.837; P=0.034). KS inhibited AAA formation and blocked the Wnt signaling pathway in AngII-infused ApoE-/- mice. CONCLUSIONS: The present study demonstrates that aberrant changes in KS expression occur in AAA. KS plays an important anti-inflammatory role and showed important clinical correlations in AAA. Decreased KS (SERPINA4) level is a risk factor of AAA rupture. Our pre-clinical animal experiments indicate that treatment with recombination KS suppresses AngII-induced aortic aneurysm formation and might be a new target for the drug therapy of AAA.

Association between plasminogen activator inhibitor­1 (PAI-1) 4G/5G polymorphism and circulating PAI-1 level in systemic lupus erythematosus and rheumatoid arthritis : A meta-analysis.

OBJECTIVE: This study systemically reviewed the evidence regarding the association between plasminogen activator inhibitor­1 (PAI­1) 4G/5G polymorphism and susceptibility to systemic lupus erythematous (SLE)/lupus nephritis (LN) and rheumatoid arthritis (RA) and the relationship between circulating PAI­1 levels and SLE/LN and RA. METHODS: We conducted a meta-analysis on the association between the PAI­1 4G/5G polymorphism and SLE/LN or RA risk and serum/plasma PAI­1 levels in patients with SLE/LN and RA and healthy controls. RESULTS: Nine articles including 657 patients with SLE and 668 controls and 567 patients with RA and 772 controls were included. No association was revealed between SLE and PAI­1 4G allele in all study subjects (odds ratio [OR] = 0.944, 95% confidence interval [CI] = 0.808-1.102, p = 0.463). Ethnicity-based stratification showed no association between the PAI­1 4G allele and SLE among Europeans and Asians. No association was detected between LN and RA and the PAI­1 4G allele (OR = 0.886, 95% CI = 0.713-1.102, p = 0.278; OR = 0.8736, 95% CI = 0.747-1.020, p = 0.088, respectively) or between SLE/LN and RA and the PAI­1 4G/5G polymorphism using the recessive and dominant models and homozygote contrast. The circulating PAI­1 level was significantly higher in the SLE group than in the control group (standardized mean difference [SMD] = 0.337, 95% CI = 0.057-0.619, p = 0.019). However, serum/plasma PAI­1 level showed no significant difference between RA and control group (SMD = 0.333, 95% CI = -0.6989-1.35, p = 0.527). CONCLUSIONS: There was no association between the PAI­1 4G/5G polymorphism and SLE/LN and RA development and significantly higher levels of circulating PAI­1 were observed in patients with SLE but not in those with RA.

Beneficial implications of sugar beet proteinase inhibitor BvSTI on plant architecture and salt stress tolerance in Lotus corniculatus L.

Food demands of increasing human population dictate intensification of livestock production, however, environmental stresses could jeopardize producers' efforts. Forage legumes suffer from yield losses and poor nutritional status due to salinity increase of agricultural soils. As tools aimed to reduce negative impacts of biotic or abiotic stresses, proteinase inhibitors (PIs) have been promoted for biotechnological improvements. In order to increase tolerance of Lotus corniculatus L. to salt stress, serine PI, BvSTI, was introduced into this legume using Agrobacterium rhizogenes, with final transformation efficiency of 4.57%. PCR, DNA gel-blot, RT-PCR and in-gel protein activity assays confirmed the presence and activity of BvSTI products in transformed lines. Plants from three selected transgenic lines (21, 73 and 109) showed significant alterations in overall phenotypic appearance, corresponding to differences in BvSTI accumulation. Lines 73 and 109 showed up to 7.3-fold higher number of tillers and massive, up to 5.8-fold heavier roots than in nontransformed controls (NTC). Line 21 was phenotypically similar to NTC, accumulated less BvSTI transcripts and did not exhibit an additional band of recombinant trypsin inhibitor as seen in lines 73 and 109. Exposure of the transgenic lines to NaCl revealed different levels of salt stress susceptibility. The NaCl sensitivity index, based on morphological appearance and chlorophyll concentrations showed that lines 73 and 109 were significantly less affected by salinity than NTC or line 21. High level of BvSTI altered morphology and delayed salt stress related senescence, implicating BvSTI gene as a promising tool for salinity tolerance improvement trials in L. corniculatus.

Alpha-1 antitrypsin treatment of new-onset type 1 diabetes: An open-label, phase I clinical trial (RETAIN) to assess safety and pharmacokinetics.

OBJECTIVE: To determine the safety and pharmacokinetics of alpha-1 antitrypsin (AAT) in adults and children. RESEARCH DESIGN AND METHODS: Short-term AAT treatment restores euglycemia in the non-obese mouse model of type 1 diabetes. A phase I multicenter study in 16 subjects with new-onset type 1 diabetes studied the safety and pharmacokinetics of Aralast NP (AAT). This open-label, dose-escalation study enrolled 8 adults aged 16 to 35 years and 8 children aged 8 to 15 years within 100 days of diagnosis, to receive 12 infusions of AAT: a low dose of 45 mg/kg weekly for 6 weeks, followed by a higher dose of 90 mg/kg for 6 weeks. RESULTS: C-peptide secretion during a mixed meal, hemoglobin A1c (HbA1c), and insulin usage remained relatively stable during the treatment period. At 72 hours after infusion of 90 mg/kg, mean levels of AAT fell below 2.0 g/L for 7 of 15 subjects. To identify a plasma level of AAT likely to be therapeutic, pharmacodynamic ex vivo assays were performed on fresh whole blood from adult subjects. Polymerase chain reaction (PCR) analyses were performed on inhibitor of IKBKE, NOD1, TLR1, and TRAD gene expression, which are important for activation of nuclear factor-κB (NF-κB) and apoptosis pathways. AAT suppressed expression dose-dependently; 50% inhibition was achieved in the 2.5 to 5.0 mg/mL range. CONCLUSIONS: AAT was well tolerated and safe in subjects with new-onset type 1 diabetes. Weekly doses of AAT greater than 90 mg/kg may be necessary for an optimal therapeutic effect.

Plasminogen activator inhibitor-1 regulates the vascular expression of vitronectin.

Essentials Vitronectin (VN) is produced by smooth muscle cells (SMCs) and promotes neointima formation. We studied the regulation of vascular VN expression by plasminogen activator inhibitor-1 (PAI-1). PAI-1 stimulates VN gene expression in SMCs by binding LDL receptor-related protein 1. Stimulation of VN gene expression may be a mechanism by which PAI-1 controls vascular remodeling. SUMMARY: Background Increased expression of vitronectin (VN) by smooth muscle cells (SMCs) promotes neointima formation after vascular injury, and may contribute to chronic vascular diseases, such as atherosclerosis. However, the molecular regulation of vascular VN expression is poorly defined. Given the overlapping expression profiles and functions of VN and plasminogen activator inhibitor (PAI)-1, we hypothesized that PAI-1 regulates vascular VN expression. Objectives To determine whether PAI-1 regulates VN expression in SMCs and in vivo. Methods The effects of genetic alterations in PAI-1 expression, pharmacologic PAI-1 inhibition and recombinant PAI-1 on SMC VN expression were studied, and vascular VN expression in wild-type (WT) and PAI-1-deficient mice was assessed. Results VN expression was significantly lower in PAI-1-deficient SMCs and significantly increased in PAI-1-overexpressing SMCs. PAI-1 small interfering RNA and pharmacologic PAI-1 inhibition significantly decreased SMC VN expression. Recombinant PAI-1 stimulated VN expression by binding LDL receptor-related protein-1 (LRP1), but another LRP1 ligand, α2 -macroglobulin, did not. As compared with WT controls, carotid artery VN expression was significantly lower in PAI-1-deficient mice and significantly higher in PAI-1-transgenic mice. In a vein graft (VG) model of intimal hyperplasia, VN expression was significantly attenuated in PAI-1-deficient VGs as compared with WT controls. The plasma VN concentration was significantly decreased in PAI-1-deficient mice versus WT controls at 4 weeks, but not at 5 days or 8 weeks, after surgery. Conclusions PAI-1 stimulates SMC VN expression by binding LRP1, and controls vascular VN expression in vivo. Autocrine regulation of vascular VN expression by PAI-1 may play important roles in vascular homeostasis and pathologic vascular remodeling.

Recombinant Trichinella pseudospiralis Serine Protease Inhibitors Alter Macrophage Polarization In Vitro.

During parasite infection, serine protease inhibitors secreted by parasites play important roles in suppressing host defenses. However, the mechanism of immune regulation is unclear. In this study, a serpin gene from Trichinella pseudospiralis, named Tp-Serpin, was cloned and expressed, in order to reveal its role in the regulation of the host immune response in T. pseudospiralis infection. The results showed that Tp-Serpin encodes a 43 kDa protein that was recognized by serum from T. pseudospiralis infected mice at 60 days post-infection (dpi). Tp-Serpin was found to be expressed at all developmental stages of T. pseudospiralis. Inhibitory activity analysis showed that recombinant Tp-Serpin (rTp-Serpin) effectively inhibited the hydrolytic activity of porcine pancreatic elastase (elastase P), human neutrophil elastase (elastase H), and mouse mast cell protease-1, but showed little inhibitory for human neutrophil cathepsin G (cathepsin G). Furthermore, rTp-Serpin induced polarization of macrophages toward the alternatively activated phenotype (M2) alone by activation of the signal transducer and activator of transcription 3 signaling pathway, and inhibited lipopolysaccharide-induced classically activation (M1) in vitro. These data preliminarily demonstrate that Tp-Serpin may play an important role in the immunoregulation of T. pseudospiralis infection by activating the M2-polarized signaling pathway.

The Potential Role of Kallistatin in the Development of Abdominal Aortic Aneurysm.

Abdominal aortic aneurysm (AAA) is a vascular condition that causes permanent dilation of the abdominal aorta, which can lead to death due to aortic rupture. The only treatment for AAA is surgical repair, and there is no current drug treatment for AAA. Aortic inflammation, vascular smooth muscle cell apoptosis, angiogenesis, oxidative stress and vascular remodeling are implicated in AAA pathogenesis. Kallistatin is a serine proteinase inhibitor, which has been shown to have a variety of functions, potentially relevant in AAA pathogenesis. Kallistatin has been reported to have inhibitory effects on tumor necrosis factor alpha (TNF-α) signaling induced oxidative stress and apoptosis. Kallistatin also inhibits vascular endothelial growth factor (VEGF) and Wnt canonical signaling, which promote inflammation, angiogenesis, and vascular remodeling in various pre-clinical experimental models. This review explores the potential protective role of kallistatin in AAA pathogenesis.

Serum vaspin levels in type 2 diabetic patients are associated with the severity of lower limb vascular lesion / 中国医师杂志

Objective To explore the association between serum vaspin levels and the severity of the lower extremity vascular lesions in type 2 diabetes mellitus (T2DM) patients.Methods According to the lower extremity artery plaque,stenosis and intima-media membrane thickening severity score,92 cases of T2DM patients were divided into three groups:simple diabetes group (DM1 group) (32 cases),mild diabetic lower limb vascular lesion group (DM2 group) (33 cases),and moderately severe diabetic lower limb vascular lesion group (DM3 group) (27 cases).Twenty-six age-and gender-matched apparently healthy controls (control group) were recruited as well.Systolic blood pressure (SBP),ankle-brachial index (ABI),insulin resistance index (HOMA-IR),and other indicators were determined,serum vaspin was measured by enzyme-linked immunosorbent assay.Results After adjustment for age and gender,the DM1 group had a significantly higher serum vaspin level than control group (P ＜0.01),while for the DM2 and DM3 groups,serum vaspin levels were significantly lower than the DM1 group (P ＜ 0.01).Partial correlation analysis showed that serum vaspin was inversely associated with HOMA-IR (r =-0.461,P =0.001)and positively correlated with ABI (r =0.462,P =0.001).Logistic regression analysis demonstrated that SBP,ABI and fasting serum vaspin levels were significantly associated with the presence of the lower extremity vascular lesions in type 2 diabetes.Conclusions Serum vaspin levels were significantly elevated in simple type 2 diabetic patients while the reduction of its level might be associated with the formation of lower extremity vascular lesions in type 2 diabetic patients.

Anti-lymphoproliferative activity of alpha-2-macroglobulin in the plasma of hibernating 13-lined ground squirrels and woodchucks.

Plasma from hibernating (HIB) woodchucks (Marmota monax) or 13-lined ground squirrels (Ictidomys tridecemlineatus) suppressed (3)H-thymidine uptake in mouse spleen cell cultures stimulated with Concanavalin A (ConA); plasma from non-hibernating animals were only slightly inhibitory. Maximum inhibition occurred when HIB plasma was added to the cultures prior to ConA. After HPLC size exclusion chromatography of the HIB ground squirrel plasma, a single fraction (fraction-14) demonstrated inhibitory activity. Assay of fraction-14 from 8 HIB squirrels showed inhibition ranging from 13 to 95%; inhibition was correlated to the time the squirrels were exposed to cold prior to hibernation. Western blot analysis showed the factor to be a large molecular weight protein (>300 kDa), and mass spectrometry identified sequences that were 100% homologous with alpha-2-macroglobulin from humans and other species. These findings indicate a hibernation-related protein that may be responsible for immune system down regulation.